Purpose:
The adult human sclera contains a network of small sized blood vessels and LYVE1+ macrophages mainly in the episclera, but lacks LYVE1+/podoplanin+ lymphatic vessels. Since it is not known whether the fetal sclera is primarily alymphatic or contains lymphatic vessels during the intrauterine scleral development, we investigate for blood and lymphatic vessels in human fetal scleral tissue at different gestational ages.

Results:
The human sclera contained CD31+ blood vessels as early as WoG 13. Until 18 WoG, the scleral stroma is enriched with blood vessels in a similar amount as the episclera (p=0.4). After 19 WoG the amount of stromal CD31+ blood vessels decreased significantly compared to episclera (p<0.02 at 19-23WoG and p<0.001 at 24-38WoG). In the lamina fusca blood vessels were absent at any time point investigated. And further, LYVE1+ or podoplanin+ lymphatic vessels were not detectable in the sclera at any gestational ages analyzed. However, single LYVE1+cells were identified primarily in the episclera their amount decreasing significantly with increasing gestational ages (12-18 WoG compared to 24-38WoG: p<0,01). In contrast to the conjunctiva where LYVE1+podoplanin+ lymphatics were detectable as early as week 17, the amount of LYVE1+cells in the sclera was highest in early pregnancy (12-18WoG), with a significant decrease during pregnancy (p<0.001).

Conclusions:
The fetal human sclera contains CD31+blood vessels as early as week 13, but is primarily alymphatic. However, single LYVE1+ cells could be identified in early pregnancy, decreasing in number with ongoing pregnancy. Compared to the conjunctiva, with high amounts of LYVE1+cells in early pregnancy and growth of lymphatic vessel as early as week 17, our findings within the sclera suggest an early and strong expression of selective antilymphangiogenic factors during development present in the sclera.